Knockout and pharmacological studies demonstrated that the activation of delta opioid peptide (DOP) receptors produces antidepressant-like effects in rodents. Here we report the results obtained with the novel DOP ligand H-Dmt-Tic-NH-CH(2)-Bid (UFP-502). UFP-502 bound with high affinity (pK(i) 9.43) to recombinant DOP receptors displaying moderate selectivity over MOP and KOP. In CHO(hDOP) [(35)S]GTPgammaS binding and mouse vas deferens experiments, UFP-502 behaved as a potent (pEC(50) 10.09 and 10.70, respectively) full agonist. In these preparations, naloxone, naltrindole and N,N(CH(3))(2)Dmt-Tic-OH showed similar pA(2) values against UFP-502 and DPDPE and the same rank order of potency. In vivo in mice, UFP-502 mimicked DPDPE actions, producing a significant reduction of immobility time after intracerebroventricular administration in the forced swimming test and a clear antinociceptive effect after intrathecal injection in the tail withdrawal assay. However, while the effects of DPDPE were fully prevented by naltrindole those evoked by UFP-502 were unaffected (tail withdrawal assay) or only partially reversed (forced swimming test). In conclusion, UFP-502 represents a novel and useful chemical template for the design of selective agonists for the DOP receptor.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.peptides.2006.07.015 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Delta opioid receptor agonists activate PI3K-mTORC1 signaling in parvalbumin-positive interneurons in mouse infralimbic prefrontal cortex to exert acute antidepressant-lie effects.
Mol Psychiatry
December 2024
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan.
Article Synopsis
- - The delta opioid receptor (DOP) is identified as a potential target for new antidepressants, as its selective agonist KNT-127 shows promise for rapid antidepressant effects while minimizing side effects.
- - In experiments, KNT-127 reduced behaviors indicative of depression, such as immobility in the forced swimming test and social avoidance in stressed mice, effects that were reversed by inhibitors of mTOR and PI3K pathways.
- - The study suggests that DOP agonists work by enhancing excitatory activity in the medial prefrontal cortex through the PI3K-Akt-mTOR signaling pathway, particularly by reducing GABA release from specific interneurons.
Dopaminergic neuronal regulation determines innate immunity of Caenorhabditis elegans during Klebsiella aerogenes infection.
Microbes Infect
October 2024
Department of Biotechnology, Science Campus, Alagappa University, Karaikudi, 630 003, India. Electronic address:
The innate immune signals are the front line of host defense against bacterial pathogens. Pathogen-induced harmful effects, such as reduced neuronal signals to the intestine, affect the host's food sensing and dwelling behavior. Here, we report that dopamine and kpc-1 signals control the intestinal innate immune responses through the p38/PMK-1 MAPK signaling pathway in C.
View Article and Find Full Text PDFUnderstanding the relationship between inflammation, apoptosis, and diabetes osteoporosis: A bioinformatics approach and experimental verification.
FASEB J
October 2024
Department of Medicine, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, People's Republic of China.
Article Synopsis
- - The study investigates diabetes osteoporosis (DOP) to find potential biomarkers and understand its mechanisms using bioinformatics tools and lab experiments.
- - Researchers identified 42 genes linked to DOP and key pathways like cytokine interactions and apoptosis, with specific emphasis on up-regulated genes such as TNF and IL6.
- - Experiments showed that high glucose levels (50 mg/mL) hindered the growth of osteoblasts (cells responsible for bone formation) and increased their apoptosis, implicating the TNF-α/FAS/FASLG signaling pathway in DOP development.
Design, Synthesis, and Characterization of Proteolytically-Stable Opioid-Neurotensin Hybrid Peptidomimetics.
ACS Pharmacol Transl Sci
September 2024
Research Group of Organic Chemistry, Departments of Chemistry and Bioengineering Sciences, Vrije Universiteit Brussel, 1050 Brussels, Belgium.
Linking an opioid to a nonopioid pharmacophore represents a promising approach for reducing opioid-induced side effects during pain management. Herein, we describe the optimization of the previously reported opioid-neurotensin hybrids (OPNT-hybrids), & , containing the μ-/δ-opioid agonist H-Dmt-d-Arg-Aba-β-Ala-NH and NT(8-13) analogs optimized for NTS2 affinity. In the present work, the constrained dipeptide Aba-β-Ala was modified to investigate the optimal linker length between the two pharmacophores, as well as the effect of expanding the aromatic moiety within constrained dipeptide analogs, via the inclusion of a naphthyl moiety.
View Article and Find Full Text PDFTreatment with quercetin mitigates polystyrene nanoparticle-induced reduction in neuron capacity by inhibiting dopaminergic neurodegeneration and facilitating dopamine metabolism in Caenorhabditis elegans.
Chemosphere
September 2024
Environment and Health research division, Public Health Research Center, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China. Electronic address:
Article Synopsis
- - Long-term exposure to nanopolystyrenes (PS-NPs) in organisms causes neurotoxicity, leading to impaired movement and sensory perception, particularly at higher concentrations.
- - In a study using the worm model Caenorhabditis elegans, quercetin was found to improve locomotion and sensory behavior while protecting against neurodegeneration caused by PS-NPs exposure, suggesting its potential as a neuroprotective agent.
- - Quercetin treatment increased dopamine levels and altered gene expression related to neurodegeneration and dopamine metabolism, indicating its role in countering PS-NPs toxicity on neuronal function.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!